Although fine needle aspiration (FNA) of thyroid nodules is the most sensitive and specific method for the detection of malignancy, a majority of patients who require surgery for a suspicion of malignancy have only an indeterminate or suspicious diagnosis cytologically. Because the distinction between benign and malignant cannot be made pre- or intra-operatively in these cases, patients with benign lesions may undergo more extensive surgery than necessary and conversely, patients with carcinoma, less than adequate initial surgery. Although various genetic alterations have been documented in thyroid neoplasms and are believed to be associated with their tumorigenesis and malignant progression, no specific alteration can reliably distinguish benign from malignant lesions. Relevant to this, the enzyme telomerase, has been reported to be reactivated in almost all malignant neoplasms, whereas its expression is repressed in almost all normal cells. Recently, the catalytic component of telomerase, human telomerase reverse transcriptase (hTERT), has been cloned and sequence. She has developed a detection method for hTERT gene expression using reverse transcriptase polymerase chain reaction (RT-PCR) and examined its expression in both thyroid nodules and FNAs. She has found that its expression correlates with telomerase enzyme activity and that the detection of hTERT is a more sensitive assay than telomerase activity. She also has found gene expression to be positive in indeterminate FNA samples from 13/14 malignant tumors, and negative in 9/10 benign tumors. The detection of hTERT gene expression in thyroid FNA samples therefore holds tremendouse pomise as a diagnostic marker of thyroid malignancy. Its application to suspicious thyroid FNA samples could dramatically alter the surgical management of patients with these lesions. Because of this, she proposes to conduct a blinded prospective multi-institutional study, examining 240 FNA samples from suspicious thyroid lesions for hTERT expression in order to estimate its sensitivity and specificity and in order to determine whether it can serve as an accurate marker of malignancy in the differential diagnosis of the suspicious thyroid nodule.